Reanalysis of "Long non‑coding RNA lung cancer‑associated transcript 1 regulates ferroptosis via microRNA‑34a‑5p‑mediated GTP cyclohydrolase 1 downregulation in lung cancer cells." by Tai, F. et al., Int J Oncol, 2024¶
Tai, F., Zhai, R., Ding, K., Zhang, Y., Yang, H., Li, H., Wang, Q., Cao, Z., Ge, C., Fu, H., Xiao, F., & Zheng, X. (2024). Long non‑coding RNA lung cancer‑associated transcript 1 regulates ferroptosis via microRNA‑34a‑5p‑mediated GTP cyclohydrolase 1 downregulation in lung cancer cells.. Int J Oncol, 64(6), .
Abstract¶
In this study, Tai et al. [1] profiled A549 cells treated with DMSO, RSL3 alone, or co-treated with Fer-1 for 24h to further our understanding of ferroptosis-associated genes in non-small cell lung cancer (NSCLC). The reanalysis of this dataset include a comprehensive RNA-seq analysis pipeline which begins with dimensionality reduction using UMAP [2], PCA [3], and t-SNE [4] to visualize sample distributions. This is followed by a clustergram heatmap to show expression patterns across samples. Differential gene expression analysis is performed for each control and perturbation pair, and the resulting gene signatures are then subjected to enrichment analysis using Enrichr [5, 6, 7]. Furthermore, transcription factor analysis of the gene signatures is conducted using ChEA3 [8]. Finally, the analysis incorporates drug match prediction using L2S2 [9] and DRUG-seqr [10] to identify both FDA-approved and non-FDA-approved compounds that can reverse or mimic the observed gene expression changes. Results are presented as tables and bar charts to facilitate interpretation.
This abstract was generated with the assistance of Gemini 2.0 Flash.
Methods¶
RNA-seq alignment
Gene count matrices were obtained from ARCHS4 [11], which preprocessed the raw FASTQ data using the Kallisto [12] and STAR [] pseudoalignment algorithm.
Gene matrix processing
The raw gene matrix was filtered to remove genes that do not have an average of 3 reads across the samples. It was then quantile, log2, and z-score normalized. A regex-based function was used to infer whether individual samples belong to a “control” or a “perturbation” group by processing the metadata associated with each sample.
Dimensionality Reduction Visualization
Three types of dimensionality reduction techniques were applied on the processed expression matrices: UMAP[2], PCA[3], and t-SNE[4]. UMAP was calculated by the UMAP Python package and PCA and t-SNE were calculated using the Scikit-Learn Python library. The samples were then represented on 2D scatterplots.
Clustergram Heatmap
As a preliminary step, the top 1000 genes exhibiting most variability were selected. Using this new set, clustergram heatmaps were generated. Two versions of the clustergram exist: an interactive one generated by Clustergrammer [13] and a publication-ready alternative.
Differentially Expressed Genes Calculation and Volcano Plot
Differentially expressed genes between the control and perturbation samples were calculated using Limma Voom [14]. The logFC and -log10p values of each gene were visualized as a volcano scatterplot. Upregulated and downregulated genes were selected according to this criteria: p < 0.05 and |logFC| > 1.0.
Enrichr Enrichment Analysis
The upregulated and down-regulated sets were separately submitted to Enrichr [5, 6, 7]. These sets were compared against libraries from ChEA [8], ARCHS4 [12], Reactome Pathways [15], MGI Mammalian Phenotype [16], Gene Ontology Biological Processes [17], GWAS Catalog [18], KEGG [19, 20, 21], and WikiPathways [22]. The top matched terms from each library and their respective -log10p values were visualized as barplots.
Chea3 Transcription Factor Analysis
The upregulated and down-regulated sets were separately submitted to Chea3 [8]. These sets were compared against the libraries ARCHS4 Coexpression [12], GTEx Coexpression [23], Enrichr [5, 6, 7], ENCODE ChIP-seq [24, 25], ReMap ChIP-seq [26], and Literature-mined ChIP-seq. The top matched TFs were ranked according to their average score across each library and represented as barplots.
L2S2 and Drug-seqr drug analysis
The top 500 up and downregulated sets were submitted simulataneously to identify reverser and mimicker molecules, both FDA and non-FDA approved, from the L2S2 [9] and Drug-seqr [10] databases. The top matched molecules were compiled into tables and visualized as barplots.
| GSM7902660 | GSM7902661 | GSM7902662 | GSM7902663 | GSM7902664 | GSM7902665 | GSM7902666 | GSM7902667 | GSM7902668 | |
|---|---|---|---|---|---|---|---|---|---|
| TSPAN6 | 507 | 530 | 530 | 581 | 536 | 517 | 566 | 579 | 619 |
| TNMD | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| DPM1 | 445 | 441 | 458 | 434 | 432 | 383 | 459 | 462 | 466 |
| SCYL3 | 221 | 230 | 232 | 261 | 238 | 226 | 238 | 297 | 245 |
| C1ORF112 | 554 | 558 | 634 | 483 | 580 | 519 | 616 | 632 | 633 |
table 1: This is a preview of the first 5 rows of the raw RNA-seq expression matrix from GSE247883.
Results¶
Dimensionality Reduction¶
UMAP¶
Figure 1: This figure displays a 2D scatter plot of a UMAP decomposition of the sample data. Each point represents an individual sample, colored by its experimental group.
PCA¶
Figure 2: This figure displays a 2D scatter plot of a PCA decomposition of the sample data. Each point represents an individual sample, colored by its experimental group.
t-SNE¶
Figure 3: This figure displays a 2D scatter plot using a t-SNE decomposition of the sample data. Each point represents an individual sample, colored by its experimental group.
Clustergram Heatmaps¶
Figure 4: The figure contains an interactive heatmap displaying gene expression for each sample in the RNA-seq dataset. Every row of the heatmap represents a gene, every column represents a sample, and every cell displays normalized gene expression values. The heatmap additionally features color bars beside each column which represent prior knowledge of each sample, such as the tissue of origin or experimental treatment.
Figure 5: this figure is a clustergram produced with the graphing library Plotly. It sacrifices some interactivity for a more polished look.
Differentially Expressed Genes Calculation and Volcano Plots¶
| logFC | AveExpr | t | P.Value | adj.P.Val | B | |
|---|---|---|---|---|---|---|
| gene_symbol | ||||||
| GRAMD1B | 0.74 | 8.93 | 33.03 | 5.954069e-17 | 9.013920e-13 | 29.05 |
| SLC7A11 | 1.01 | 9.21 | 32.92 | 6.302118e-17 | 9.013920e-13 | 29.07 |
| SQSTM1 | 0.59 | 9.05 | 27.02 | 1.745352e-15 | 1.328005e-11 | 25.81 |
| TXNRD1 | 0.40 | 10.02 | 26.92 | 1.856959e-15 | 1.328005e-11 | 25.62 |
| AKR1C3 | 2.11 | 5.73 | 23.36 | 1.984020e-14 | 1.135098e-10 | 20.59 |
Table 2: This is a preview of the first 5 rows of the differentially expressed gene table calculated by Limma Voom.
| logFC | AveExpr | t | P.Value | adj.P.Val | B | |
|---|---|---|---|---|---|---|
| gene_symbol | ||||||
| GRAMD1B | 0.96 | 9.04 | 42.15 | 3.314248e-19 | 6.153087e-15 | 34.21 |
| EGFR | 0.39 | 11.97 | 41.52 | 4.301955e-19 | 6.153087e-15 | 33.20 |
| TXNRD1 | 0.60 | 10.11 | 37.63 | 2.417543e-18 | 1.855332e-14 | 32.29 |
| GPRC5A | 0.84 | 9.50 | 37.32 | 2.786586e-18 | 1.855332e-14 | 32.21 |
| SLC7A11 | 1.25 | 9.32 | 37.00 | 3.242907e-18 | 1.855332e-14 | 32.05 |
Table 3: This is a preview of the first 5 rows of the differentially expressed gene table calculated by Limma Voom.
cells dmso h rep-vs-cells rsl fer h rep
Figure 6: The figure contains an interactive scatter plot which displays the log2-fold changes and statistical significance of each gene calculated by performing a differential gene expression analysis for the comparison cells dmso h rep-vs-cells rsl fer h rep. Every point in the plot represents a gene. Red points indicate significantly up-regulated genes, blue points indicate down-regulated genes.
cells dmso h rep-vs-cells rsl h rep
Figure 7: The figure contains an interactive scatter plot which displays the log2-fold changes and statistical significance of each gene calculated by performing a differential gene expression analysis for the comparison cells dmso h rep-vs-cells rsl h rep. Every point in the plot represents a gene. Red points indicate significantly up-regulated genes, blue points indicate down-regulated genes.
Enrichr: Enrichment Analysis¶
Upregulated Set¶
cells dmso h rep-vs-cells rsl fer h rep¶
Figure 8: This figure contains several barplots depicting enrichment analysis results on the upregulated gene set. Each barplot corresponds to an individual library from Enrichr, and the top matching terms by p-value are depicted in each. Statistically significant terms are represented as red bars while others are represented as gray. Access your Enrichment results here: https://amp.pharm.mssm.edu/Enrichr/enrich?dataset=37688fa2cdb8fd824ac139fe44ac4f5a
cells dmso h rep-vs-cells rsl h rep¶
Figure 9: This figure contains several barplots depicting enrichment analysis results on the upregulated gene set. Each barplot corresponds to an individual library from Enrichr, and the top matching terms by p-value are depicted in each. Statistically significant terms are represented as red bars while others are represented as gray. Access your Enrichment results here: https://amp.pharm.mssm.edu/Enrichr/enrich?dataset=f46cc8b3b6124d04b1e2ec6f647579ea
Downregulated Set¶
cells dmso h rep-vs-cells rsl fer h rep¶
Figure 10: This figure contains several barplots depicting enrichment analysis results on the upregulated gene set. Each barplot corresponds to an individual library from Enrichr, and the top matching terms by p-value are depicted in each. Statistically significant terms are represented as red bars while others are represented as gray. Access your Enrichment results here: https://amp.pharm.mssm.edu/Enrichr/enrich?dataset=f46cc8b3b6124d04b1e2ec6f647579ea
cells dmso h rep-vs-cells rsl h rep¶
Figure 11: This figure contains several barplots depicting enrichment analysis results on the upregulated gene set. Each barplot corresponds to an individual library from Enrichr, and the top matching terms by p-value are depicted in each. Statistically significant terms are represented as red bars while others are represented as gray. Access your Enrichment results here: https://amp.pharm.mssm.edu/Enrichr/enrich?dataset=f46cc8b3b6124d04b1e2ec6f647579ea
CHEA3: Transcription Factor Enrichment Analysis¶
Upregulated Set¶
cells dmso h rep-vs-cells rsl fer h rep¶
Figure 12: Horizontal bar chart, y-axis represents transcription factors. Displays the top ranked transcription factors for the upregulated set according to their average integrated scores across all the libraries.
cells dmso h rep-vs-cells rsl h rep¶
Figure 13: Horizontal bar chart, y-axis represents transcription factors. Displays the top ranked transcription factors for the upregulated set according to their average integrated scores across all the libraries.
Downregulated Set¶
cells dmso h rep-vs-cells rsl fer h rep¶
Figure 14: Horizontal bar chart, y-axis represents transcription factors. Displays the top ranked transcription factors for the upregulated set according to their average integrated scores across all the libraries.
cells dmso h rep-vs-cells rsl h rep¶
Figure 15: Horizontal bar chart, y-axis represents transcription factors. Displays the top ranked transcription factors for the upregulated set according to their average integrated scores across all the libraries.
L2S2 and DRUG-seqr: Reverser and Mimicker Drugs¶
Reverser Results¶
cells dmso h rep-vs-cells rsl fer h rep¶
l2s2_fda
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | trametinib | PBIOA004_XC.L10_24H_K06_trametinib_2.22uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | True | 1552 |
| 1 | selumetinib | ASG003_XC.P909_24H_E04_selumetinib_10uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | True | 2242 |
| 2 | afatinib | ASG003_XC.P914_24H_M20_afatinib_1.11uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 2348 |
| 3 | acyclovir | REP.A008_MCF7_24H_E06_acyclovir_0.04uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 290 |
| 4 | selumetinib | REP.A015_A375_24H_E19_selumetinib_10uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 2242 |
| 5 | trametinib | PBIOA004_XC.R10_24H_K04_trametinib_20uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 1552 |
| 6 | dinoprostone | FIBR026_MCLF141SZ_6H_M12_dinoprostone_4uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 138 |
| 7 | selumetinib | ASG003_XC.P091_24H_E05_selumetinib_1.11uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 2242 |
| 8 | selumetinib | LJP006_A549_24H_M07_selumetinib_10uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 2242 |
| 9 | trametinib | ASG003_XC.P911_24H_N18_trametinib_0.12uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 1552 |
| 10 | thioridazine | CPC006_HCC515_6H_G23_thioridazine_10uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 1444 |
| 11 | selumetinib | LKCP001_A549_24H_J10_selumetinib_10uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 2242 |
| 12 | trametinib | PBIOA004_XC.L10_24H_K04_trametinib_20uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 13 | chlorotrianisene | PAC003_U2OS_6H_F14_chlorotrianisene_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 28 |
| 14 | trametinib | ASG003_XC.P909_24H_N18_trametinib_0.12uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 15 | trametinib | ASG002_NCIH1573_24H_G09_trametinib_0.12uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 16 | famotidine | PAC004_U2OS_6H_B06_famotidine_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 332 |
| 17 | trametinib | LCP001_MCF10A.WT_3H_D16_trametinib_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 18 | thalidomide | CPC006_A549_6H_E14_thalidomide_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 850 |
| 19 | dasatinib | LJP007_HT29_24H_G14_dasatinib_3.33uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 3026 |
Table 4: Ranked FDA-approved LINCS L1000 signatures predicted to reverse the uploaded geneset.
Figure 16: barplot representation depicting the -log10p values of the top FDA-approved l2s2_fda reversers. Red bars represent statistically significant results; otherwise gray.
l2s2_all
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | PD-0325901 | LGR001_XC.L100.L_96H_H06_PD-0325901_0.04uM up | 1.57e-13 | 2.63e-07 | 3.98e+00 | 42 | False | 3630 |
| 1 | BRD-K85051645 | CPC007_MCF7_6H_M06_BRD-K85051645_10uM up | 3.10e-12 | 2.60e-06 | 3.78e+00 | 40 | False | 58 |
| 2 | BIIB-021 | REP.A016_MDAMB231_24H_D22_BIIB-021_0.37uM up | 1.31e-11 | 4.41e-06 | 3.67e+00 | 39 | False | 346 |
| 3 | PD-0325901 | LGR001_XC.L100.L_120H_H01_PD-0325901_10uM up | 1.31e-11 | 4.41e-06 | 3.67e+00 | 39 | False | 3630 |
| 4 | XL-888 | ASG003_XC.P908_24H_L14_XL-888_1.11uM up | 1.31e-11 | 4.41e-06 | 3.67e+00 | 39 | False | 878 |
| 5 | PD-0325901 | LGR001_XC.L100.M_72H_H02_PD-0325901_3.33uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 3630 |
| 6 | XL-888 | ASG003_XC.P907_24H_L14_XL-888_1.11uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 878 |
| 7 | PD-0325901 | LGR001_XC.L100.M_72H_H05_PD-0325901_0.125uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 3630 |
| 8 | BRD-K82710617 | MOA001_A549_24H_G05_BRD-K82710617_10uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 16 |
| 9 | SH3BP5 up | XPR014_U251MG.311_96H_E11_SH3BP5 up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 150 |
| 10 | BRD-K26347562 | MOA001_A549_24H_K21_BRD-K26347562_10uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 196 |
| 11 | trametinib | PBIOA004_XC.L10_24H_K06_trametinib_2.22uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | True | 1552 |
| 12 | vemurafenib | LJP005_MDAMB231_24H_C16_vemurafenib_0.37uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1862 |
| 13 | BRD-K00824317 | PAC004_U2OS_6H_B09_BRD-K00824317_4uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 40 |
| 14 | AZ-628 | LJP001_MDAMB231_24H_J12_AZ-628_0.08uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1618 |
| 15 | TNFRSF1A up | XPR028_A549.311_96H_C03_TNFRSF1A up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 84 |
| 16 | NVP-AUY922 | ASG003_XC.P907_24H_M14_NVP-AUY922_1.11uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1158 |
| 17 | BRD-K12244279 | PBIOA015_A549_24H_K04_BRD-K12244279_0.37uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 204 |
| 18 | PRIMA1 | MOA001_A549_24H_I19_PRIMA1_10uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 218 |
| 19 | AZ-628 | ASG003_A549_48H_J14_AZ-628_1.11uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1618 |
Table 5: Ranked LINCS L1000 signatures predicted to reverse the uploaded geneset.
Figure 17: barplot representation depicting the -log10p values of the top l2s2_all reversers. Red bars represent statistically significant results; otherwise gray.
drugseqr_fda
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid28... | 5.96e-02 | 1 | 1.58e+00 | 15 | True | 110 |
| 1 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid40... | 1.97e-01 | 1 | 1.34e+00 | 12 | True | 110 |
| 2 | bosutinib | Bosutinib_FA-10-SN61_batchid16_10uM_24h up | 2.07e-01 | 1 | 1.37e+00 | 10 | True | 8 |
| 3 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.86e-01 | 1 | 1.23e+00 | 12 | True | 110 |
| 4 | tirbanibulin | Tirbanibulin_AD-86-OB87_batchid6_0.1uM_24h up | 3.74e-01 | 1 | 1.15e+00 | 11 | True | 8 |
| 5 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid3_... | 4.34e-01 | 1 | 1.13e+00 | 7 | True | 110 |
| 6 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid16... | 7.22e-01 | 1 | 8.27e-01 | 4 | True | 110 |
| 7 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid44... | 8.30e-01 | 1 | 7.68e-01 | 8 | True | 110 |
| 8 | temozolomide | Temozolomide_BA-92-YC70_batchid20_10uM_24h up | 8.31e-01 | 1 | 5.72e-01 | 1 | True | 4 |
| 9 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid23... | 9.21e-01 | 1 | 6.31e-01 | 6 | True | 110 |
Table 6: Ranked FDA-approved DRUG-seq signatures predicted to reverse the uploaded geneset.
Figure 18: barplot representation depicting the -log10p values of the top FDA-approved drugseqr_fda reversers. Red bars represent statistically significant results; otherwise gray.
drugseqr_all
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid28... | 5.96e-02 | 1 | 1.58e+00 | 15 | True | 110 |
| 1 | cephalochromin | Cephalochromin_QA-14-AU91_batchid40_10uM_24h up | 1.13e-01 | 1 | 1.37e+00 | 19 | False | 5 |
| 2 | 24995756 | 24995756_CE-03-YQ91_batchid16_10uM_24h up | 1.20e-01 | 1 | 1.49e+00 | 12 | False | 6 |
| 3 | tp-472 | TP-472_HB-87-YY34_batchid28_10uM_24h up | 1.63e-01 | 1 | 1.59e+00 | 7 | False | 7 |
| 4 | _HB-92-PE54_batchid52_10uM_24h up | 1.91e-01 | 1 | 1.80e+00 | 4 | False | 8 | |
| 5 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid40... | 1.97e-01 | 1 | 1.34e+00 | 12 | True | 110 |
| 6 | bosutinib | Bosutinib_FA-10-SN61_batchid16_10uM_24h up | 2.07e-01 | 1 | 1.37e+00 | 10 | True | 8 |
| 7 | pik-iii | Pik-III_EB-47-BB89_batchid16_10uM_24h up | 2.12e-01 | 1 | 1.93e+00 | 3 | False | 7 |
| 8 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.86e-01 | 1 | 1.23e+00 | 12 | True | 110 |
| 9 | pi4kiiibeta-in-9 | PI4KIIIbeta-IN-9_PD-71-MW24_batchid24_10uM_24h up | 3.09e-01 | 1 | 1.33e+00 | 6 | False | 7 |
| 10 | tx1-85-1 | TX1-85-1_S0-EE-YMWJ_batchid32_10uM_24h up | 3.33e-01 | 1 | 1.29e+00 | 6 | False | 6 |
| 11 | cathepsin g inhibitor i | Cathepsin G Inhibitor I_PD-60-FM93_batchid16_1... | 3.63e-01 | 1 | 1.20e+00 | 8 | False | 7 |
| 12 | tirbanibulin | Tirbanibulin_AD-86-OB87_batchid6_0.1uM_24h up | 3.74e-01 | 1 | 1.15e+00 | 11 | True | 8 |
| 13 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid3_... | 4.34e-01 | 1 | 1.13e+00 | 7 | True | 110 |
| 14 | _BD-11-DV28_batchid32_10uM_24h up | 4.76e-01 | 1 | 1.12e+00 | 5 | False | 104 | |
| 15 | _BD-11-DV28_batchid48_10uM_24h up | 4.88e-01 | 1 | 1.10e+00 | 5 | False | 104 | |
| 16 | _BD-11-DV28_batchid33_10uM_24h up | 5.17e-01 | 1 | 1.04e+00 | 8 | False | 104 | |
| 17 | mefloquine | Mefloquine_FA-16-HR75_batchid16_10uM_24h up | 5.20e-01 | 1 | 1.04e+00 | 7 | False | 8 |
| 18 | _BD-11-DV28_batchid29_10uM_24h up | 5.25e-01 | 1 | 1.03e+00 | 10 | False | 104 | |
| 19 | 46184988 | 46184988_DE-69-QQ25_batchid32_10uM_24h up | 5.90e-01 | 1 | 9.75e-01 | 11 | False | 5 |
Table 7: Ranked DRUG-seq signatures predicted to reverse the uploaded geneset.
Figure 19: barplot representation depicting the -log10p values of the top drugseqr_all reversers. Red bars represent statistically significant results; otherwise gray.
cells dmso h rep-vs-cells rsl h rep¶
l2s2_fda
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | trametinib | PBIOA004_XC.L10_24H_K06_trametinib_2.22uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | True | 1552 |
| 1 | selumetinib | ASG003_XC.P909_24H_E04_selumetinib_10uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | True | 2242 |
| 2 | afatinib | ASG003_XC.P914_24H_M20_afatinib_1.11uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 2348 |
| 3 | acyclovir | REP.A008_MCF7_24H_E06_acyclovir_0.04uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 290 |
| 4 | selumetinib | REP.A015_A375_24H_E19_selumetinib_10uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 2242 |
| 5 | trametinib | PBIOA004_XC.R10_24H_K04_trametinib_20uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 1552 |
| 6 | dinoprostone | FIBR026_MCLF141SZ_6H_M12_dinoprostone_4uM up | 8.27e-10 | 3.22e-05 | 3.37e+00 | 36 | True | 138 |
| 7 | selumetinib | ASG003_XC.P091_24H_E05_selumetinib_1.11uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 2242 |
| 8 | selumetinib | LJP006_A549_24H_M07_selumetinib_10uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 2242 |
| 9 | trametinib | ASG003_XC.P911_24H_N18_trametinib_0.12uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 1552 |
| 10 | thioridazine | CPC006_HCC515_6H_G23_thioridazine_10uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 1444 |
| 11 | selumetinib | LKCP001_A549_24H_J10_selumetinib_10uM up | 3.07e-09 | 7.16e-05 | 3.27e+00 | 35 | True | 2242 |
| 12 | trametinib | PBIOA004_XC.L10_24H_K04_trametinib_20uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 13 | chlorotrianisene | PAC003_U2OS_6H_F14_chlorotrianisene_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 28 |
| 14 | trametinib | ASG003_XC.P909_24H_N18_trametinib_0.12uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 15 | trametinib | ASG002_NCIH1573_24H_G09_trametinib_0.12uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 16 | famotidine | PAC004_U2OS_6H_B06_famotidine_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 332 |
| 17 | trametinib | LCP001_MCF10A.WT_3H_D16_trametinib_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 1552 |
| 18 | thalidomide | CPC006_A549_6H_E14_thalidomide_10uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 850 |
| 19 | dasatinib | LJP007_HT29_24H_G14_dasatinib_3.33uM up | 1.11e-08 | 1.47e-04 | 3.17e+00 | 34 | True | 3026 |
Table 8: Ranked FDA-approved LINCS L1000 signatures predicted to reverse the uploaded geneset.
Figure 20: barplot representation depicting the -log10p values of the top FDA-approved l2s2_fda reversers. Red bars represent statistically significant results; otherwise gray.
l2s2_all
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | PD-0325901 | LGR001_XC.L100.L_96H_H06_PD-0325901_0.04uM up | 1.57e-13 | 2.63e-07 | 3.98e+00 | 42 | False | 3630 |
| 1 | BRD-K85051645 | CPC007_MCF7_6H_M06_BRD-K85051645_10uM up | 3.10e-12 | 2.60e-06 | 3.78e+00 | 40 | False | 58 |
| 2 | BIIB-021 | REP.A016_MDAMB231_24H_D22_BIIB-021_0.37uM up | 1.31e-11 | 4.41e-06 | 3.67e+00 | 39 | False | 346 |
| 3 | PD-0325901 | LGR001_XC.L100.L_120H_H01_PD-0325901_10uM up | 1.31e-11 | 4.41e-06 | 3.67e+00 | 39 | False | 3630 |
| 4 | XL-888 | ASG003_XC.P908_24H_L14_XL-888_1.11uM up | 1.31e-11 | 4.41e-06 | 3.67e+00 | 39 | False | 878 |
| 5 | PD-0325901 | LGR001_XC.L100.M_72H_H02_PD-0325901_3.33uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 3630 |
| 6 | XL-888 | ASG003_XC.P907_24H_L14_XL-888_1.11uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 878 |
| 7 | PD-0325901 | LGR001_XC.L100.M_72H_H05_PD-0325901_0.125uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 3630 |
| 8 | BRD-K82710617 | MOA001_A549_24H_G05_BRD-K82710617_10uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 16 |
| 9 | SH3BP5 up | XPR014_U251MG.311_96H_E11_SH3BP5 up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 150 |
| 10 | BRD-K26347562 | MOA001_A549_24H_K21_BRD-K26347562_10uM up | 5.40e-11 | 8.24e-06 | 3.57e+00 | 38 | False | 196 |
| 11 | trametinib | PBIOA004_XC.L10_24H_K06_trametinib_2.22uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | True | 1552 |
| 12 | vemurafenib | LJP005_MDAMB231_24H_C16_vemurafenib_0.37uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1862 |
| 13 | BRD-K00824317 | PAC004_U2OS_6H_B09_BRD-K00824317_4uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 40 |
| 14 | AZ-628 | LJP001_MDAMB231_24H_J12_AZ-628_0.08uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1618 |
| 15 | TNFRSF1A up | XPR028_A549.311_96H_C03_TNFRSF1A up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 84 |
| 16 | NVP-AUY922 | ASG003_XC.P907_24H_M14_NVP-AUY922_1.11uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1158 |
| 17 | BRD-K12244279 | PBIOA015_A549_24H_K04_BRD-K12244279_0.37uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 204 |
| 18 | PRIMA1 | MOA001_A549_24H_I19_PRIMA1_10uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 218 |
| 19 | AZ-628 | ASG003_A549_48H_J14_AZ-628_1.11uM up | 2.15e-10 | 1.64e-05 | 3.47e+00 | 37 | False | 1618 |
Table 9: Ranked LINCS L1000 signatures predicted to reverse the uploaded geneset.
Figure 21: barplot representation depicting the -log10p values of the top l2s2_all reversers. Red bars represent statistically significant results; otherwise gray.
drugseqr_fda
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid28... | 5.96e-02 | 1 | 1.58e+00 | 15 | True | 110 |
| 1 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid40... | 1.97e-01 | 1 | 1.34e+00 | 12 | True | 110 |
| 2 | bosutinib | Bosutinib_FA-10-SN61_batchid16_10uM_24h up | 2.07e-01 | 1 | 1.37e+00 | 10 | True | 8 |
| 3 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.86e-01 | 1 | 1.23e+00 | 12 | True | 110 |
| 4 | tirbanibulin | Tirbanibulin_AD-86-OB87_batchid6_0.1uM_24h up | 3.74e-01 | 1 | 1.15e+00 | 11 | True | 8 |
| 5 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid3_... | 4.34e-01 | 1 | 1.13e+00 | 7 | True | 110 |
| 6 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid16... | 7.22e-01 | 1 | 8.27e-01 | 4 | True | 110 |
| 7 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid44... | 8.30e-01 | 1 | 7.68e-01 | 8 | True | 110 |
| 8 | temozolomide | Temozolomide_BA-92-YC70_batchid20_10uM_24h up | 8.31e-01 | 1 | 5.72e-01 | 1 | True | 4 |
| 9 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid23... | 9.21e-01 | 1 | 6.31e-01 | 6 | True | 110 |
Table 10: Ranked FDA-approved DRUG-seq signatures predicted to reverse the uploaded geneset.
Figure 22: barplot representation depicting the -log10p values of the top FDA-approved drugseqr_fda reversers. Red bars represent statistically significant results; otherwise gray.
drugseqr_all
| perturbation | term | pvalueReverse | adjPvalueReverse | oddsRatioReverse | reverserOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid28... | 5.96e-02 | 1 | 1.58e+00 | 15 | True | 110 |
| 1 | cephalochromin | Cephalochromin_QA-14-AU91_batchid40_10uM_24h up | 1.13e-01 | 1 | 1.37e+00 | 19 | False | 5 |
| 2 | 24995756 | 24995756_CE-03-YQ91_batchid16_10uM_24h up | 1.20e-01 | 1 | 1.49e+00 | 12 | False | 6 |
| 3 | tp-472 | TP-472_HB-87-YY34_batchid28_10uM_24h up | 1.63e-01 | 1 | 1.59e+00 | 7 | False | 7 |
| 4 | _HB-92-PE54_batchid52_10uM_24h up | 1.91e-01 | 1 | 1.80e+00 | 4 | False | 8 | |
| 5 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid40... | 1.97e-01 | 1 | 1.34e+00 | 12 | True | 110 |
| 6 | bosutinib | Bosutinib_FA-10-SN61_batchid16_10uM_24h up | 2.07e-01 | 1 | 1.37e+00 | 10 | True | 8 |
| 7 | pik-iii | Pik-III_EB-47-BB89_batchid16_10uM_24h up | 2.12e-01 | 1 | 1.93e+00 | 3 | False | 7 |
| 8 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.86e-01 | 1 | 1.23e+00 | 12 | True | 110 |
| 9 | pi4kiiibeta-in-9 | PI4KIIIbeta-IN-9_PD-71-MW24_batchid24_10uM_24h up | 3.09e-01 | 1 | 1.33e+00 | 6 | False | 7 |
| 10 | tx1-85-1 | TX1-85-1_S0-EE-YMWJ_batchid32_10uM_24h up | 3.33e-01 | 1 | 1.29e+00 | 6 | False | 6 |
| 11 | cathepsin g inhibitor i | Cathepsin G Inhibitor I_PD-60-FM93_batchid16_1... | 3.63e-01 | 1 | 1.20e+00 | 8 | False | 7 |
| 12 | tirbanibulin | Tirbanibulin_AD-86-OB87_batchid6_0.1uM_24h up | 3.74e-01 | 1 | 1.15e+00 | 11 | True | 8 |
| 13 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid3_... | 4.34e-01 | 1 | 1.13e+00 | 7 | True | 110 |
| 14 | _BD-11-DV28_batchid32_10uM_24h up | 4.76e-01 | 1 | 1.12e+00 | 5 | False | 104 | |
| 15 | _BD-11-DV28_batchid48_10uM_24h up | 4.88e-01 | 1 | 1.10e+00 | 5 | False | 104 | |
| 16 | _BD-11-DV28_batchid33_10uM_24h up | 5.17e-01 | 1 | 1.04e+00 | 8 | False | 104 | |
| 17 | mefloquine | Mefloquine_FA-16-HR75_batchid16_10uM_24h up | 5.20e-01 | 1 | 1.04e+00 | 7 | False | 8 |
| 18 | _BD-11-DV28_batchid29_10uM_24h up | 5.25e-01 | 1 | 1.03e+00 | 10 | False | 104 | |
| 19 | 46184988 | 46184988_DE-69-QQ25_batchid32_10uM_24h up | 5.90e-01 | 1 | 9.75e-01 | 11 | False | 5 |
Table 11: Ranked DRUG-seq signatures predicted to reverse the uploaded geneset.
Figure 23: barplot representation depicting the -log10p values of the top drugseqr_all reversers. Red bars represent statistically significant results; otherwise gray.
Mimicker Results¶
cells dmso h rep-vs-cells rsl fer h rep¶
l2s2_fda
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | crizotinib | ASG003_XC.P914_24H_I04_crizotinib_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | True | 1884 |
| 1 | sonidegib | FIBR011_MCLF015CN_6H_E03_sonidegib_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | True | 502 |
| 2 | ingenol-mebutate | REP.B027_HEK293_24H_D22_ingenol-mebutate_0.08u... | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 310 |
| 3 | dabrafenib | ASG002_MKN45_24H_K24_dabrafenib_0.12uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 1304 |
| 4 | sonidegib | FIBR010_MCLF123SZ_6H_E03_sonidegib_4uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 502 |
| 5 | dabrafenib | ASG003_XC.P091_24H_H18_dabrafenib_0.12uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 1304 |
| 6 | raloxifene | ASG003_XC.P904_24H_I13_raloxifene_10uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 1452 |
| 7 | fluphenazine | PAC066_U2OS_6H_B24_fluphenazine_20uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 750 |
| 8 | trifluoperazine | PAC004_U2OS_6H_A14_trifluoperazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 1388 |
| 9 | cyt-387 | LJP005_A549_24H_P08_CYT-387_3.33uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 772 |
| 10 | fluphenazine | PAC001_U2OS_6H_K24_fluphenazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 750 |
| 11 | ingenol | HOG001_A549_24H_B16_ingenol_1.11uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 214 |
| 12 | thioridazine | PAC067_U2OS_6H_L01_thioridazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 1444 |
| 13 | tretinoin | FIBR010_MCLF123SZ_6H_B03_tretinoin_4uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 988 |
| 14 | ingenol-mebutate | REP.B027_HELA_24H_D20_ingenol-mebutate_0.74uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 310 |
| 15 | trifluoperazine | PAC006_U2OS_6H_A14_trifluoperazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 1388 |
| 16 | ingenol-mebutate | REP.B027_HELA_24H_D21_ingenol-mebutate_0.25uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 310 |
| 17 | ingenol-mebutate | REP.B027_HELA_24H_D22_ingenol-mebutate_0.08uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 310 |
| 18 | carbamazepine | KTOX002_HPTEC_6H_N13_carbamazepine_1000uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 638 |
| 19 | nilotinib | LKCP001_A549_24H_G01_nilotinib_10uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 1230 |
Table 12: Ranked FDA-approved LINCS L1000 signatures predicted to mimic the uploaded geneset.
Figure 24: barplot representation depicting the -log10p values of the top FDA-approved l2s2_fda mimickers. Red bars represent statistically significant results; otherwise gray.
l2s2_all
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | quizartinib | ASG003_XC.P915_24H_F10_quizartinib_10uM up | 1.00e-17 | 1.68e-11 | 4.61e+00 | 48 | False | 1482 |
| 1 | TL-HRAS-61 | MOA001_A549_24H_G11_TL-HRAS-61_10uM up | 3.38e-14 | 2.83e-08 | 4.09e+00 | 43 | False | 434 |
| 2 | CGS-15943 | ASG003_XC.P091_24H_K13_CGS-15943_10uM up | 1.57e-13 | 8.78e-08 | 3.98e+00 | 42 | False | 712 |
| 3 | BRD-K67526586 | ERG012_PC3_6H_O17_BRD-K67526586_10uM up | 7.09e-13 | 2.38e-07 | 3.88e+00 | 41 | False | 16 |
| 4 | KIN-001-220 | LJP009_SKL.C_24H_F13_KIN-001-220_10uM up | 7.09e-13 | 2.38e-07 | 3.88e+00 | 41 | False | 650 |
| 5 | crizotinib | ASG003_XC.P914_24H_I04_crizotinib_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | True | 1884 |
| 6 | BRD-K68313733 | CPC007_HT29_6H_I03_BRD-K68313733_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 64 |
| 7 | IL3RA up | XPR018_ES2.311_96H_G16_IL3RA up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 40 |
| 8 | parbendazole | MOA001_A549_24H_P04_parbendazole_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 904 |
| 9 | fenbendazole | MOA001_A549_24H_O03_fenbendazole_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 126 |
| 10 | BRD-A15079084 | HOG001_A549_6H_G22_BRD-A15079084_0.002uM up | 1.31e-11 | 2.01e-06 | 3.67e+00 | 39 | False | 202 |
| 11 | PX-12 | FIBR027_MCLF130CN_6H_E18_PX-12_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 508 |
| 12 | parbendazole | MOA001_A549_24H_O04_parbendazole_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 904 |
| 13 | calmidazolium | CPC014_A549_6H_J20_calmidazolium_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 174 |
| 14 | sonidegib | FIBR011_MCLF015CN_6H_E03_sonidegib_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | True | 502 |
| 15 | BRD-K51556300 | CPC019_HT29_6H_P22_BRD-K51556300_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 82 |
| 16 | BRD-A15079084 | HOG001_A549_6H_G14_BRD-A15079084_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 202 |
| 17 | QS-11 | FIBR011_MCLF015CN_6H_K12_QS-11_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 212 |
| 18 | ingenol-mebutate | REP.B027_HEK293_24H_D22_ingenol-mebutate_0.08u... | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 310 |
| 19 | BRD-K56411643 | MOA001_A549_24H_C03_BRD-K56411643_10uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | False | 178 |
Table 13: Ranked LINCS L1000 signatures predicted to mimic the uploaded geneset.
Figure 25: barplot representation depicting the -log10p values of the top l2s2_all mimickers. Red bars represent statistically significant results; otherwise gray.
drugseqr_fda
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.02e-06 | 4.19e-03 | 2.81e+00 | 27 | True | 110 |
| 1 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid3_... | 4.78e-06 | 5.72e-03 | 3.31e+00 | 20 | True | 110 |
| 2 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid28... | 1.20e-05 | 1.26e-02 | 2.67e+00 | 25 | True | 110 |
| 3 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid40... | 1.31e-05 | 1.33e-02 | 2.72e+00 | 24 | True | 110 |
| 4 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid23... | 3.15e-05 | 2.30e-02 | 2.58e+00 | 24 | True | 110 |
| 5 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid16... | 3.31e-05 | 2.35e-02 | 3.40e+00 | 16 | True | 110 |
| 6 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid44... | 4.99e-05 | 3.09e-02 | 2.44e+00 | 25 | True | 110 |
| 7 | bosutinib | Bosutinib_FA-10-SN61_batchid16_10uM_24h up | 5.38e-05 | 3.15e-02 | 2.78e+00 | 20 | True | 8 |
| 8 | temozolomide | Temozolomide_BA-92-YC70_batchid20_10uM_24h up | 7.03e-05 | 3.72e-02 | 5.42e+00 | 9 | True | 4 |
| 9 | tirbanibulin | Tirbanibulin_AD-86-OB87_batchid6_0.1uM_24h up | 1.05e-04 | 4.79e-02 | 2.44e+00 | 23 | True | 8 |
Table 14: Ranked FDA-approved DRUG-seq signatures predicted to mimic the uploaded geneset.
Figure 26: barplot representation depicting the -log10p values of the top FDA-approved drugseqr_fda mimickers. Red bars represent statistically significant results; otherwise gray.
drugseqr_all
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | _BD-11-DV28_batchid9_10uM_24h up | 2.67e-08 | 7.02e-04 | 3.77e+00 | 25 | False | 104 | |
| 1 | _GE-53-SM76_batchid35_1uM_24h up | 6.97e-08 | 9.17e-04 | 4.63e+00 | 19 | False | 7 | |
| 2 | 11591924 | 11591924_FB-95-JD99_batchid20_10uM_24h up | 2.54e-07 | 1.79e-03 | 3.86e+00 | 21 | False | 5 |
| 3 | mefloquine | Mefloquine_FA-16-HR75_batchid16_10uM_24h up | 3.26e-07 | 1.79e-03 | 3.52e+00 | 23 | False | 8 |
| 4 | 46184988 | 46184988_DE-69-QQ25_batchid32_10uM_24h up | 3.40e-07 | 1.79e-03 | 2.80e+00 | 31 | False | 5 |
| 5 | galeterone | Galeterone_BD-36-VB52_batchid20_10uM_24h up | 5.24e-07 | 2.30e-03 | 5.13e+00 | 15 | False | 6 |
| 6 | pi4kiiibeta-in-9 | PI4KIIIbeta-IN-9_PD-71-MW24_batchid24_10uM_24h up | 8.35e-07 | 3.14e-03 | 4.11e+00 | 18 | False | 7 |
| 7 | staurosporine | Staurosporine_AA-58-FJ71_batchid13_0.01uM_24h up | 1.24e-06 | 3.75e-03 | 2.49e+00 | 34 | False | 8 |
| 8 | tx1-85-1 | TX1-85-1_S0-EE-YMWJ_batchid32_10uM_24h up | 1.28e-06 | 3.75e-03 | 3.98e+00 | 18 | False | 6 |
| 9 | inflachromene | Inflachromene_GD-72-XO18_batchid44_10uM_24h up | 1.47e-06 | 3.87e-03 | 2.00e+01 | 6 | False | 6 |
| 10 | zygosporin a | Zygosporin A_BE-42-IC00_batchid40_10uM_24h up | 1.78e-06 | 4.19e-03 | 2.36e+00 | 36 | False | 8 |
| 11 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.02e-06 | 4.19e-03 | 2.81e+00 | 27 | True | 110 |
| 12 | 9807391 | 9807391_AD-00-WA10_batchid28_10uM_24h up | 2.13e-06 | 4.19e-03 | 2.00e+00 | 49 | False | 6 |
| 13 | _QC-76-GI57_batchid36_10uM_24h up | 2.23e-06 | 4.19e-03 | 4.87e+00 | 14 | False | 5 | |
| 14 | _BD-11-DV28_batchid32_10uM_24h up | 3.25e-06 | 5.61e-03 | 3.91e+00 | 17 | False | 104 | |
| 15 | _BD-11-DV28_batchid35_10uM_24h up | 3.41e-06 | 5.61e-03 | 2.88e+00 | 25 | False | 104 | |
| 16 | cephalochromin | Cephalochromin_QA-14-AU91_batchid40_10uM_24h up | 3.84e-06 | 5.63e-03 | 2.40e+00 | 33 | False | 5 |
| 17 | imd-0354 | Imd-0354_LB-65-SM65_batchid32_10uM_24h up | 4.03e-06 | 5.63e-03 | 2.85e+00 | 25 | False | 8 |
| 18 | cathepsin g inhibitor i | Cathepsin G Inhibitor I_PD-60-FM93_batchid16_1... | 4.26e-06 | 5.63e-03 | 3.22e+00 | 21 | False | 7 |
| 19 | lly-507 | Lly-507_AE-52-NW93_batchid20_10uM_24h up | 4.28e-06 | 5.63e-03 | 2.18e+00 | 39 | False | 4 |
Table 15: Ranked DRUG-seq signatures predicted to mimic the uploaded geneset.
Figure 27: barplot representation depicting the -log10p values of the top drugseqr_all mimickers. Red bars represent statistically significant results; otherwise gray.
cells dmso h rep-vs-cells rsl h rep¶
l2s2_fda
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | crizotinib | ASG003_XC.P914_24H_I04_crizotinib_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | True | 1884 |
| 1 | sonidegib | FIBR011_MCLF015CN_6H_E03_sonidegib_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | True | 502 |
| 2 | ingenol-mebutate | REP.B027_HEK293_24H_D22_ingenol-mebutate_0.08u... | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 310 |
| 3 | dabrafenib | ASG002_MKN45_24H_K24_dabrafenib_0.12uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 1304 |
| 4 | sonidegib | FIBR010_MCLF123SZ_6H_E03_sonidegib_4uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 502 |
| 5 | dabrafenib | ASG003_XC.P091_24H_H18_dabrafenib_0.12uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 1304 |
| 6 | raloxifene | ASG003_XC.P904_24H_I13_raloxifene_10uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 1452 |
| 7 | fluphenazine | PAC066_U2OS_6H_B24_fluphenazine_20uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 750 |
| 8 | trifluoperazine | PAC004_U2OS_6H_A14_trifluoperazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 1388 |
| 9 | cyt-387 | LJP005_A549_24H_P08_CYT-387_3.33uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 772 |
| 10 | fluphenazine | PAC001_U2OS_6H_K24_fluphenazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 750 |
| 11 | ingenol | HOG001_A549_24H_B16_ingenol_1.11uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 214 |
| 12 | thioridazine | PAC067_U2OS_6H_L01_thioridazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 1444 |
| 13 | tretinoin | FIBR010_MCLF123SZ_6H_B03_tretinoin_4uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 988 |
| 14 | ingenol-mebutate | REP.B027_HELA_24H_D20_ingenol-mebutate_0.74uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 310 |
| 15 | trifluoperazine | PAC006_U2OS_6H_A14_trifluoperazine_20uM up | 8.27e-10 | 2.10e-05 | 3.37e+00 | 36 | True | 1388 |
| 16 | ingenol-mebutate | REP.B027_HELA_24H_D21_ingenol-mebutate_0.25uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 310 |
| 17 | ingenol-mebutate | REP.B027_HELA_24H_D22_ingenol-mebutate_0.08uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 310 |
| 18 | carbamazepine | KTOX002_HPTEC_6H_N13_carbamazepine_1000uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 638 |
| 19 | nilotinib | LKCP001_A549_24H_G01_nilotinib_10uM up | 3.07e-09 | 5.37e-05 | 3.27e+00 | 35 | True | 1230 |
Table 16: Ranked FDA-approved LINCS L1000 signatures predicted to mimic the uploaded geneset.
Figure 28: barplot representation depicting the -log10p values of the top FDA-approved l2s2_fda mimickers. Red bars represent statistically significant results; otherwise gray.
l2s2_all
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | quizartinib | ASG003_XC.P915_24H_F10_quizartinib_10uM up | 1.00e-17 | 1.68e-11 | 4.61e+00 | 48 | False | 1482 |
| 1 | TL-HRAS-61 | MOA001_A549_24H_G11_TL-HRAS-61_10uM up | 3.38e-14 | 2.83e-08 | 4.09e+00 | 43 | False | 434 |
| 2 | CGS-15943 | ASG003_XC.P091_24H_K13_CGS-15943_10uM up | 1.57e-13 | 8.78e-08 | 3.98e+00 | 42 | False | 712 |
| 3 | BRD-K67526586 | ERG012_PC3_6H_O17_BRD-K67526586_10uM up | 7.09e-13 | 2.38e-07 | 3.88e+00 | 41 | False | 16 |
| 4 | KIN-001-220 | LJP009_SKL.C_24H_F13_KIN-001-220_10uM up | 7.09e-13 | 2.38e-07 | 3.88e+00 | 41 | False | 650 |
| 5 | crizotinib | ASG003_XC.P914_24H_I04_crizotinib_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | True | 1884 |
| 6 | BRD-K68313733 | CPC007_HT29_6H_I03_BRD-K68313733_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 64 |
| 7 | IL3RA up | XPR018_ES2.311_96H_G16_IL3RA up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 40 |
| 8 | parbendazole | MOA001_A549_24H_P04_parbendazole_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 904 |
| 9 | fenbendazole | MOA001_A549_24H_O03_fenbendazole_10uM up | 3.10e-12 | 5.20e-07 | 3.78e+00 | 40 | False | 126 |
| 10 | BRD-A15079084 | HOG001_A549_6H_G22_BRD-A15079084_0.002uM up | 1.31e-11 | 2.01e-06 | 3.67e+00 | 39 | False | 202 |
| 11 | PX-12 | FIBR027_MCLF130CN_6H_E18_PX-12_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 508 |
| 12 | parbendazole | MOA001_A549_24H_O04_parbendazole_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 904 |
| 13 | calmidazolium | CPC014_A549_6H_J20_calmidazolium_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 174 |
| 14 | sonidegib | FIBR011_MCLF015CN_6H_E03_sonidegib_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | True | 502 |
| 15 | BRD-K51556300 | CPC019_HT29_6H_P22_BRD-K51556300_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 82 |
| 16 | BRD-A15079084 | HOG001_A549_6H_G14_BRD-A15079084_10uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 202 |
| 17 | QS-11 | FIBR011_MCLF015CN_6H_K12_QS-11_4uM up | 5.40e-11 | 5.04e-06 | 3.57e+00 | 38 | False | 212 |
| 18 | ingenol-mebutate | REP.B027_HEK293_24H_D22_ingenol-mebutate_0.08u... | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | True | 310 |
| 19 | BRD-K56411643 | MOA001_A549_24H_C03_BRD-K56411643_10uM up | 2.15e-10 | 1.03e-05 | 3.47e+00 | 37 | False | 178 |
Table 17: Ranked LINCS L1000 signatures predicted to mimic the uploaded geneset.
Figure 29: barplot representation depicting the -log10p values of the top l2s2_all mimickers. Red bars represent statistically significant results; otherwise gray.
drugseqr_fda
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.02e-06 | 4.19e-03 | 2.81e+00 | 27 | True | 110 |
| 1 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid3_... | 4.78e-06 | 5.72e-03 | 3.31e+00 | 20 | True | 110 |
| 2 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid28... | 1.20e-05 | 1.26e-02 | 2.67e+00 | 25 | True | 110 |
| 3 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid40... | 1.31e-05 | 1.33e-02 | 2.72e+00 | 24 | True | 110 |
| 4 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid23... | 3.15e-05 | 2.30e-02 | 2.58e+00 | 24 | True | 110 |
| 5 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid16... | 3.31e-05 | 2.35e-02 | 3.40e+00 | 16 | True | 110 |
| 6 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid44... | 4.99e-05 | 3.09e-02 | 2.44e+00 | 25 | True | 110 |
| 7 | bosutinib | Bosutinib_FA-10-SN61_batchid16_10uM_24h up | 5.38e-05 | 3.15e-02 | 2.78e+00 | 20 | True | 8 |
| 8 | temozolomide | Temozolomide_BA-92-YC70_batchid20_10uM_24h up | 7.03e-05 | 3.72e-02 | 5.42e+00 | 9 | True | 4 |
| 9 | tirbanibulin | Tirbanibulin_AD-86-OB87_batchid6_0.1uM_24h up | 1.05e-04 | 4.79e-02 | 2.44e+00 | 23 | True | 8 |
Table 18: Ranked FDA-approved DRUG-seq signatures predicted to mimic the uploaded geneset.
Figure 30: barplot representation depicting the -log10p values of the top FDA-approved drugseqr_fda mimickers. Red bars represent statistically significant results; otherwise gray.
drugseqr_all
| perturbation | term | pvalueMimic | adjPvalueMimic | oddsRatioMimic | mimickerOverlap | approved | count | |
|---|---|---|---|---|---|---|---|---|
| 0 | _BD-11-DV28_batchid9_10uM_24h up | 2.67e-08 | 7.02e-04 | 3.77e+00 | 25 | False | 104 | |
| 1 | _GE-53-SM76_batchid35_1uM_24h up | 6.97e-08 | 9.17e-04 | 4.63e+00 | 19 | False | 7 | |
| 2 | 11591924 | 11591924_FB-95-JD99_batchid20_10uM_24h up | 2.54e-07 | 1.79e-03 | 3.86e+00 | 21 | False | 5 |
| 3 | mefloquine | Mefloquine_FA-16-HR75_batchid16_10uM_24h up | 3.26e-07 | 1.79e-03 | 3.52e+00 | 23 | False | 8 |
| 4 | 46184988 | 46184988_DE-69-QQ25_batchid32_10uM_24h up | 3.40e-07 | 1.79e-03 | 2.80e+00 | 31 | False | 5 |
| 5 | galeterone | Galeterone_BD-36-VB52_batchid20_10uM_24h up | 5.24e-07 | 2.30e-03 | 5.13e+00 | 15 | False | 6 |
| 6 | pi4kiiibeta-in-9 | PI4KIIIbeta-IN-9_PD-71-MW24_batchid24_10uM_24h up | 8.35e-07 | 3.14e-03 | 4.11e+00 | 18 | False | 7 |
| 7 | staurosporine | Staurosporine_AA-58-FJ71_batchid13_0.01uM_24h up | 1.24e-06 | 3.75e-03 | 2.49e+00 | 34 | False | 8 |
| 8 | tx1-85-1 | TX1-85-1_S0-EE-YMWJ_batchid32_10uM_24h up | 1.28e-06 | 3.75e-03 | 3.98e+00 | 18 | False | 6 |
| 9 | inflachromene | Inflachromene_GD-72-XO18_batchid44_10uM_24h up | 1.47e-06 | 3.87e-03 | 2.00e+01 | 6 | False | 6 |
| 10 | zygosporin a | Zygosporin A_BE-42-IC00_batchid40_10uM_24h up | 1.78e-06 | 4.19e-03 | 2.36e+00 | 36 | False | 8 |
| 11 | omacetaxine mepesuccinate | Omacetaxine Mepesuccinate_EA-18-FP00_batchid6_... | 2.02e-06 | 4.19e-03 | 2.81e+00 | 27 | True | 110 |
| 12 | 9807391 | 9807391_AD-00-WA10_batchid28_10uM_24h up | 2.13e-06 | 4.19e-03 | 2.00e+00 | 49 | False | 6 |
| 13 | _QC-76-GI57_batchid36_10uM_24h up | 2.23e-06 | 4.19e-03 | 4.87e+00 | 14 | False | 5 | |
| 14 | _BD-11-DV28_batchid32_10uM_24h up | 3.25e-06 | 5.61e-03 | 3.91e+00 | 17 | False | 104 | |
| 15 | _BD-11-DV28_batchid35_10uM_24h up | 3.41e-06 | 5.61e-03 | 2.88e+00 | 25 | False | 104 | |
| 16 | cephalochromin | Cephalochromin_QA-14-AU91_batchid40_10uM_24h up | 3.84e-06 | 5.63e-03 | 2.40e+00 | 33 | False | 5 |
| 17 | imd-0354 | Imd-0354_LB-65-SM65_batchid32_10uM_24h up | 4.03e-06 | 5.63e-03 | 2.85e+00 | 25 | False | 8 |
| 18 | cathepsin g inhibitor i | Cathepsin G Inhibitor I_PD-60-FM93_batchid16_1... | 4.26e-06 | 5.63e-03 | 3.22e+00 | 21 | False | 7 |
| 19 | lly-507 | Lly-507_AE-52-NW93_batchid20_10uM_24h up | 4.28e-06 | 5.63e-03 | 2.18e+00 | 39 | False | 4 |
Table 19: Ranked DRUG-seq signatures predicted to mimic the uploaded geneset.
Figure 31: barplot representation depicting the -log10p values of the top drugseqr_all mimickers. Red bars represent statistically significant results; otherwise gray.
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